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Inhibition of astrocytic DRD2 suppresses CNS inflammation in an animal model of multiple sclerosis

ABSTRACT: Inhibition of astrocytic DRD2 suppresses CNS inflammation in an animal model of multiple sclerosis

PROVIDER: PRJNA844329 | ENA |

REPOSITORIES: ENA

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Inhibition of astrocytic DRD2 suppresses CNS inflammation in an animal model of multiple sclerosis [astrocyte]

Project description:Astrocyte activation is associated with progressive inflammatory demyelination in multiple sclerosis (MS). The molecular mechanisms underlying astrocyte activation remain incompletely understood. Recent studies have suggested that classical neurotransmitter receptors are implicated in the modulation of brain innate immunity. We investigated the role of dopamine signaling in the process of astrocyte activation. Here, we show the upregulation of dopamine D2 receptor (DRD2) in reactive astrocytes in MS brain and non-canonical role of astrocytic DRD2 in MS pathogenesis. Mice deficient in astrocytic Drd2 exhibit a remarkable suppression of reactive astrocytes and inflammation which are highly correlated with the amelioration of experimental autoimmune encephalomyelitis (EAE). Mechanistically, DRD2 regulates the expression of 6-pyruvoyl-tetrahydropterin synthase which modulates NF-κB activity through protein kinase C-δ. Pharmacological blockade of astrocytic DRD2 with a DRD2 antagonist dehydrocorybulbine remarkably inhibits the inflammatory response in mice lacking Drd2 in neurons. Together, our findings reveal previously uncharted roles for a DRD2 in astrocyte activation during EAE-associated CNS inflammation. Its therapeutic inhibition may provide a potent lever to alleviate autoimmune diseases.

2022-07-15 | GSE205290 | GEO

Inhibition of astrocytic DRD2 suppresses CNS inflammation in an animal model of multiple sclerosis [spinal cord]

2022-07-15 | GSE205291 | GEO

Inhibition of astrocytic DRD2 suppresses CNS inflammation in an animal model of multiple sclerosis [astrocyte]

Project description:Inhibition of astrocytic DRD2 suppresses CNS inflammation in an animal model of multiple sclerosis [astrocyte]

| PRJNA844335 | ENA

Inhibition of astrocytic DRD2 suppresses CNS inflammation in an animal model of multiple sclerosis [spinal cord]

Project description:Inhibition of astrocytic DRD2 suppresses CNS inflammation in an animal model of multiple sclerosis [spinal cord]

| PRJNA844336 | ENA

Inhibition of astrocytic DRD2 suppresses CNS inflammation in an animal model of multiple sclerosis

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-07-15 | GSE205292 | GEO

kaempferitrin-induced secretome analyses in rat CTX TNA2 astrocytic cell line

Project description:Kaempferitrin is extracted at significant quantity from leaves of Cinnamomum osmophloeum. People consuming extract containing kaempferitrin often happen to be of high risk for diabetes and neurodegenerative diseases. For kaempferitrin to be used every day for them, the systematic effect, especially on immune system and on the CNS, needs to be addressed. In this project we used astrocytic cell line as a model to test the differentially regulated secretomes, to test kaemfperitrin effect on CNS glia.

2017-11-24 | PXD002814 | Pride

Expression data from Drd2+ cells of mouse mPFC

Project description:The heterogeneity of cortical dopamine D2 receptor expressing cells is not well characterized We performed microarrays to study expression of all the transcriprts specifically from Drd2+ neurons of mouse mPFC. For this we immunoprecipitated ribosomes from mPFC of D2Cre::RiboTag mouse, where ribosomal subunit Rpl22 is tagged with HA epitope specifically in Drd2+ neurons

2018-06-16 | GSE115887 | GEO

Gene Expression Signature in Rat Pituitary MMQ Cells Treated With DRD2 agonist UNC9994

Project description:DRD2 agonists are effective in treating pituitary tumors. To fathom the β-arresin-dependent mechanisms underlying DRD2-mediated pituitary tumor growth suppression,we applied RNA-seq analysis to rat pituitary MMQ cells treated with a DRD2 β-arresin-biased agoinst, UNC9994.MMQ cells were treated with UNC9994(15μM) or vehecle control for 12 h or 24 h and then subject to RNA-seq analysis.We found oxidative-stress-related genes such as Nqo1 and Hmox1 were upregulated by UNC9994, revealing oxidative stress may be the basis of UNC9994-induced tumor growth suppression. Our study represents the first detailed analysis of transcriptomes in rat pituitary MMQ cells treated with DRD2 β-arresin-biased agonist.The significance of altered expression of specific transcripts will enhance our understanding of DRD2 signaling in pituitary tumor cells.

2023-07-13 | GSE154351 | GEO

Gene expression data from hippocampus, striatum, hypothalamus cortex, Drd2-MSNs and Drd1-MSNs in mice

Project description:Goal of the experiment: Analysis of gene expression changes in the cortex, striatum, hippocampus, hypothalamus, Drd2-MSNs and Drd1-MSNs of mice with a postnatal, neuron-specific ablation of GLP or G9a as compared to control mice. For microarray analysis, hippocampus, hypothalamus, cortex and striatum of Camk2a-Cre; GLPfl/fl, Camk2a-Cre; G9afl/fl and age (10-14 week old) and sex matched littermate controls were used for total RNA purification. Four biological replicates were performed for each experiment. Polyribosome associated mRNAs from five, age (10-14 week old) and sex matched Drd1-Cre; Drd1-bacTRAP; G9afl/fl, or Drd2-Cre; Drd2-bacTRAP; G9afl/fl and Drd1-bacTRAP; G9afl/fl or Drd2-bacTRAP; G9afl/fl control mice were used. Three biological replicates were performed for each experiment.

2009-12-10 | E-GEOD-19402 | biostudies-arrayexpress

Microarray analysis of WT and Drd2-/- striatal tissue from C57BL/6 mice

Project description:Drd2 regulates striatal gene networks.

2012-10-25 | GSE41638 | GEO